Review
Biochemistry & Molecular Biology
Yi Teng, Yuhang Chen, Xinyi Tang, Shengjun Wang, Kai Yin
Summary: In this review, the role of PAD2-mediated citrullination in tumor pathology and the regulation of tumor-associated immune cells is systematically illustrated. The article also discusses the feasibility of anti-PAD2 therapy to treat tumors and the urgent problems to be solved. Finally, recent developments in the development of PAD2 inhibitors are reviewed.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Plant Sciences
Claudius Marondedze, Giuliano Elia, Ludivine Thomas, Aloysius Wong, Chris Gehring
Summary: The study reveals that the proteome of Arabidopsis thaliana contains proteins with a specific citrullination signature, many of which have nucleotide-binding regulatory functions, and that changes in the citrullinome occur in response to cold stress. It also identifies an A. thaliana protein with peptidyl arginine deiminase activity that is calcium-dependent for many peptide substrates, highlighting the importance of this post-translational modification in cellular reprogramming during stress responses.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Cell Biology
Mohamed Gijon, Rachael L. Metheringham, Michael S. Toss, Samantha J. Paston, Lindy G. Durrant
Summary: The study found that high expression of cytoplasmic PADI2, PADI4, and nuclear PADI4 in colorectal cancer patients was associated with an increase in overall survival.
Review
Immunology
Yoke Chan Chow, Hok Chai Yam, Baskaran Gunasekaran, Weng Yeen Lai, Weng Yue Wo, Tarun Agarwal, Yien Yien Ong, Siew Lee Cheong, Sheri-Ann Tan
Summary: Porphyromonas gingivalis, a major pathogenic bacterium involved in periodontitis, utilizes gingipain R and bacterial peptidyl arginine deiminase to citrullinate host proteins, leading to the development of non-communicable diseases. Inhibiting these enzymes can provide new therapeutic solutions for periodontitis and diseases involving bacterial citrullination.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Immunology
Dongwei Zhu, Wei Song, Zehui Jiang, Haopeng Zhou, Shengjun Wang
Summary: Citrullination is a reaction that converts arginine residues in protein peptide chains to citrulline residues. It plays a regulatory role in various physiological processes and is also implicated in the development of autoimmune diseases.
CLINICAL IMMUNOLOGY
(2022)
Review
Cell Biology
Sambit K. Nanda, Stefan Vollmer, Ana B. Perez-Oliva
Summary: This review summarizes classical post-translational modifications (PTMs) such as phosphorylation, ubiquitylation, and SUMOylation of the different components of NLRP3 and other emerging inflammasomes. The importance of these modifications in the biology, function, and regulation of these multiprotein complexes in various immune processes and human diseases is highlighted. Less-studied modifications and disease-associated mutations affecting PTMs are also discussed. The review concludes by emphasizing how a deeper understanding of different PTMs can contribute to the development of biomarkers and identification of novel drug targets for diseases associated with inflammasome malfunctioning.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Aneta Stachowicz, Alia Sadiq, Brian Walker, Niveda Sundararaman, Justyna Fert-Bober
Summary: This study revealed that the treatment with BB-Cl leads to increased expression of HO-1 through the Nrf2 pathway, which can prevent excessive tissue damage and provide substantial clinical benefits for the treatment of cardiac fibrosis.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Immunology
Maria Teresa Martin Monreal, Alexandra Stripp Rebak, Laura Massarenti, Santanu Mondal, Ladislav Senolt, Niels Odum, Michael L. Nielsen, Paul R. Thompson, Claus H. Nielsen, Dres Damgaard
Summary: Citrullination plays a role in breaking self-tolerance in anti-CCP-positive rheumatoid arthritis, with PAD2 and PAD4 being key pathogenic factors. Inhibitors like AFM-30a and GSK199 show potential in inhibiting citrullination, with AFM-30a being an efficient inhibitor of PAD2 and a combination of AFM-30a and GSK199 showing promise in inhibiting PAD activity without cytotoxic effects seen in BB-Cl-amidine.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Yi-Fang Yang, Chien-Yun Lee, Ju-Yi Hsieh, Yi-Liang Liu, Chi-Li Lin, Guang-Yaw Liu, Hui-Chih Hung
Summary: This study uncovers a mechanism where PAD4 mediates the citrullination of AZ protein, regulating polyamine homeostasis by upregulating cellular levels of ODC and polyamines. This mechanism may have significant implications in cancer biology.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Multidisciplinary Sciences
Maria A. A. Christophorou
Summary: Post-translational modification of proteins, particularly citrullination mediated by peptidylarginine deiminase (PAD) enzymes, plays a vital role in regulating the proteome. While the biochemistry of PAD activation has been extensively studied in vitro, the mechanisms regulating PADIs within cells are not well understood.
ROYAL SOCIETY OPEN SCIENCE
(2022)
Article
Immunology
Karen Yu, Luna Dillemans, Mieke Gouwy, Helena Bessa, Mieke Metzemaekers, Erik Martens, Patrick Matthys, Xavier Bossuyt, Patrick Verschueren, Carine Wouters, Lien De Somer, Paul Proost
Summary: In this study, a fluorescent in vitro assay was improved to characterize endogenous PAD activity in complex samples. The results showed similar levels of PAD activity in synovial fluids of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) patients, while citrullination was limited in joints of patients with gout or Lyme's disease. Interestingly, a higher level of extracellular citrullination was only found in blood of anti-CCP-positive RA patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Yi-Hang Song, Zhi-Jie Wang, Le Kang, Zi-Xuan He, Sheng-Bing Zhao, Xue Fang, Zhao-Shen Li, Shu-Ling Wang, Yu Bai
Summary: PADs are enzymes that deiminate arginine residues into citrulline in proteins, which is an important post-translational modification involved in various physiological and pathological processes. NETs are generated by NETosis, a type of cell death in neutrophils, and play both beneficial and detrimental roles in inflammation. Excessive activation of PADs and NETs is crucial in the progression from physiological to pathological conditions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Sheri-Ann Tan, Hok Chai Yam, Siew Lee Cheong, Yoke Chan Chow, Chui Yin Bok, Jia Min Ho, Pei Yin Lee, Baskaran Gunasekaran
Summary: This study evaluated the inhibitory activity of Cratoxylym cochinchinense leaves extract on PPAD. The results demonstrated that the extract exhibited high antioxidant potential and contained abundant phenolic and flavonoid compounds. In vitro and in vivo experiments showed dose-dependent inhibition of PPAD by the extract. Molecular docking simulation suggested potential phytochemicals responsible for the observed inhibitory activities.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Leonard Barasa, Sauradip Chaudhuri, Jeffrey Y. Zhou, Zhaozhao Jiang, Shruti Choudhary, Robert Madison Green, Elenore Wiggin, Michael Cameron, Fiachra Humphries, Katherine A. Fitzgerald, Paul R. Thompson
Summary: The cGMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway is crucial for detecting cytosolic dsDNA and triggering inflammatory response. Aberrant STING activation is associated with diseases such as ALS, lupus, AGS, and SAVI. In this study, we developed LB244 as a highly potent and selective inhibitor of STING signaling, which showed efficacy comparable to BB-Cl-amidine in vivo. These findings suggest a potential therapeutic approach for STING-dependent inflammatory diseases.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Biology
Jack P. C. Williams, Louise J. Walport
Summary: PADI6 is a maternal factor that plays a crucial role in early embryonic development. Despite being less well-characterized, it has been suggested to have various functions in the early mouse embryo. In order to understand its crucial role in early embryo development and female fertility, key outstanding questions regarding its molecular mechanisms must be answered.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Review
Infectious Diseases
Simone M. Caccio, Marco Lalle, Staffan G. Svard
INFECTION GENETICS AND EVOLUTION
(2018)
Article
Cell Biology
Nahuel Zamponi, Emiliano Zamponi, Gonzalo F. Mayol, Adriana Lanfredi-Rangel, Staffan G. Svard, Maria C. Touz
Article
Infectious Diseases
Showgy Y. Ma'ayeh, Jingyi Liu, Dimitra Peirasmaki, Katarina Hornaeus, Sara Bergstrom Mlind, Manfred Grabherr, Jonas Bergquist, Staffan G. Svard
PLOS NEGLECTED TROPICAL DISEASES
(2017)
Article
Parasitology
M. Guadalupe Ortega-Pierres, Aaron R. Jex, Brendan R. E. Ansell, Staffan G. Svard
Article
Infectious Diseases
Johan Ankarklev, Marianne Lebbad, Elin Einarsson, Oscar Franzen, Harri Ahola, Karin Troell, Staffan G. Svard
INFECTION GENETICS AND EVOLUTION
(2018)
Article
Multidisciplinary Sciences
Lorena S. Frontera, Sofia Moyano, Gonzalo Quassollo, Adriana Lanfredi-Rangel, Andrea S. Ropolo, Maria C. Touz
SCIENTIFIC REPORTS
(2018)
Article
Genetics & Heredity
Feifei Xu, Alejandro Jimenez-Gonzalez, Elin Einarsson, Asgeir Astvaldsson, Dimitra Peirasmaki, Lars Eckmann, Jan O. Andersson, Staffan G. Svard, Jon Jerlstrom-Hultqvist
MICROBIAL GENOMICS
(2020)
Review
Parasitology
Maria Romina Rivero, Constanza Feliziani, Carlos De Angelo, Karina Tiranti, Oscar Daniel Salomon, Maria Carolina Touz
PARASITOLOGY RESEARCH
(2020)
Editorial Material
Parasitology
Laura Rojas-Lopez, Rafael C. Marques, Staffan G. Svard
TRENDS IN PARASITOLOGY
(2022)
Article
Microbiology
Jorik M. van Rijn, Jens Eriksson, Jana Gruttner, Magnus Sundbom, Dominic-Luc Webb, Per M. Hellstrom, Staffan G. Svard, Mikael E. Sellin
Summary: Understanding the dynamic interactions between individual microbes and host cells is crucial for infectious disease research. A new method for live-cell imaging of microbial infection dynamics on human intestinal epithelial cell layers has been developed, providing insights into the behavior of Salmonella and Giardia pathogens.
Article
Genetics & Heredity
Laura Rojas-Lopez, Sascha Krakovka, Elin Einarsson, Ulf Ribacke, Feifei Xu, Jon Jerlstrom-Hultqvist, Staffan G. Svard
Summary: Giardia intestinalis, an intestinal protozoan parasite causing diarrheal infections worldwide, undergoes significant gene expression changes during late encystation, with major up-regulation of cyst wall proteins and sequential up-regulation of transcription factors. This high-resolution gene expression map of Giardia encystation provides valuable insights for further studies of this important differentiation process.
Article
Biology
Rui Santos, Asgeir Astvaldsson, Shweta Pipaliya, Jon Paulin Zumthor, Joel B. Dacks, Staffan Svard, Adrian B. Hehl, Carmen Faso
Summary: This study presents a quantitative morphological characterization of Giardia lamblia's endocytic system using volumetric electron microscopy and super-resolution microscopy. The study also compared endosome-like organelles in phylogenetically related taxa. The findings shed light on the evolution of GlACLC analogues in the Fornicata supergroup and their possible role in the formation and maintenance of stable clathrin assemblies at PVs in Giardia.
Article
Biology
Lubos Voleman, Vladimira Najdrova, Asgeir Astvaldsson, Pavla Tumova, Elin Einarsson, Zdenek Svindrych, Guy M. Hagen, Jan Tachezy, Staffan G. Svard, Pavel Dolezal
Article
Immunology
Kurt Hanevik, Einar Kristoffersen, Kristine Morch, Kristin Paulsen Rye, Steinar Sornes, Staffan Svard, Oystein Bruserud, Nina Langeland
Article
Microbiology
Jorik M. van Rijn, Jens Eriksson, Jana Gruttner, Magnus Sundbom, Dominic-Luc Webb, Per M. Hellstrom, Staffan G. Svard, Mikael E. Sellin
Summary: The study focuses on dynamic interactions between pathogenic microbes and host tissues, utilizing live-cell microscopy to visualize microbe behavior on intestinal epithelial cell (IEC) layers. By imaging without fluorescent labels, the method provides high-resolution observation of Salmonella and Giardia interactions on the epithelial surface, revealing pathogen-specific swimming patterns and stages of infection cycles previously unrecognized. This relatively inexpensive approach bridges the divide between technical requirements for live-cell imaging and physiological infection niche parameters.